We propose that excessive phagocytosis by pulmonary macrophages, during which drooling of normal intralysosomal components takes place into the extracellular space, leads to the degranulation of mast cells and the release of histamine in the alveolar space adjacent to the area in which excessive macrophage phagocytosis is taking place. The histamine increases the permeability of the microcirculation; thereby creating a local edema, which is nature's method of flooding an injured area with complement. If the size and intensity of this response is not overwhelming, the edema fluids will drain away from the lung; if not, increasing edema will develop and in time even Adult Respiratory Distress Syndrome. In preliminary studies we have isolated from aqueous extracts of acetone powder of lung a factor which increases the permeability of the microcirculation of rat skin (Blueing reaction) as well as produces local hemorrhage and pitting edema in rat lung when introduced via tracheotomy. This pulmonary permeability factor (PPF) is completely inhibited by either pepstatin or large amounts of antihistamine. PPF is found in the lyosomal fraction of whole lung and is particularly rich in macrophages obtained by pulmonary washout. The specific aims of this project are: 1) To isolate PPF in quantity and stable form utilizing ultrafiltration, ion exchange chromatography, etc. 2) To characterize PPF as to amino acid composition, carbohydrate content, and identify of N-terminal amino acid. 3) To check PPF for enzymatic activity against various substrates. 4) to determine the kinetics of the increase in rat lung permeability produced by PPF using colloidal carbon as a tracer. We will also determine the effect of 48/80 (a mast cell degranulator) as well as antihistamines in terms of the inhibition of PPF produced lung edema.